We have recently investigated chemical components of embryo of the lotus, Nelumbo nucifera Gaertner, to isolate a new alkaloid (4) along with known alkaloids such as Neferine. We have also investigated inhibitory activity of some alkaloids of Nelumbo nucifera on locomotor activity. In this symposium we will present an asymmetric synthesis of the new alkaloid 4 and related compounds. New alkaloid 4 and streoisomers of Neferine (17-19) were synthesized by using Gawley asymmetric alkylation and Ullmann coupling as key reactions. Asymmetric alkylation of tetrahydroisoquinoline 11, bearing an oxazoline as chiral auxiliary, with chloride 10 in THF at -98℃ gave 12 in 99% of diastereoselectivity. Ullmann coupling of 14 and 15 which was synthesized by the same alkylation procedure was achieved by using cuprous bromide-dimethyl sulfide and cesium carbonate in refluxing pyridine to give bisbenzylisoquinoline 16. Deprotection of 16 gave the new alkaloid 4. By the same methodology, three streoisomers of Neferine (17-19) were also synthesized. In order to synthesize O-methylneferine (5), we have developed new diastereoselective Pictet-Spengler cycliztion reaction of urea 24 bearing 1-(1-naphthyl)ethyl group as chiral auxiliary. Reaction of 24 with aldehyde 25 in the presence of trifluoroacetic acid in dichloromethane proceeded at -20℃ to give, after silica gel column chromatography, tetrahydroisoquinoline 26 in 65% isolated yield along with 34% yield of the diastereomer. O-Methylneferine was also synthesized by Ullmann coupling of 27 with corresponding bromide which wasl alst synthesized by this Pctet-Spengler reaction. Pharmacological activity of these alkaloids was evaluated to show inhibition of locomotor activity in mice.
